Rexulti (Brexpiprazole) Overview

• Rexulti is a prescription medication used to treat certain mental health conditions, including depression.
• This medication may cause side effects such as weight gain, drowsiness, and restlessness. More severe adverse effects are possible but uncommon.
• Rexulti can interact with some other drugs, including certain antibiotics.

Rexulti is prescribed for:

• major depressive disorder (MDD) in adults when used along with an antidepressant
• schizophrenia in adults and some pediatric patients
• agitation associated with dementia due to Alzheimer’s disease in adults

For the agitation indication, Rexulti is intended for daily use rather than as an as-needed medication when agitation occurs.

To read more about Rexulti’s indications, see the “Is Rexulti used for depression?” and “Does Rexulti have other uses?” sections below.

Note: As a person’s condition changes, they may need assistance understanding details of their treatment. This article includes information that caregivers may find helpful regarding Rexulti.

Rexulti medication basics

Rexulti’s active component is brexpiprazole. (The active component is the ingredient responsible for a drug’s therapeutic effects.) There is no generic version of Rexulti available.

Clinical trials have shown Rexulti to be effective and generally safe for treating depression, schizophrenia, and agitation related to Alzheimer’s disease.

What are Rexulti’s side effects?

As with most medications, Rexulti can cause both mild and serious side effects. The lists below cover some of the more commonly reported effects but are not exhaustive. Your prescriber or pharmacist can provide the full list of potential side effects.

Remember that side effects may vary depending on:

• your age
• existing medical conditions
• concurrent medications

Your healthcare provider or pharmacist can explain the possible adverse effects of Rexulti and suggest ways to minimize them.

Note: The Food and Drug Administration (FDA) monitors and collects reports of side effects after a drug is approved. Reporting your experience can help improve medication safety. If you experience a side effect while taking Rexulti and wish to notify the FDA, visit MedWatch or call 800-332-1088.

Mild side effects

Below are some mild side effects that have been reported with Rexulti. For additional mild effects, consult your prescriber, pharmacist, or Rexulti’s prescribing information.

Reported mild side effects include:

• weight gain
• drowsiness
• akathisia (a sense of restlessness)
• nasopharyngitis (common cold)
• headache
• constipation
• vivid dreams or insomnia
• fatigue

Mild side effects often resolve within days to a few weeks. If they persist or interfere with daily life, speak with your healthcare provider.

Serious side effects

Serious reactions to Rexulti can happen but are uncommon. Contact your prescriber promptly if you experience any serious symptoms. For suspected medical emergencies, call 911 or your local emergency number.

Serious side effects that have been linked to Rexulti include:

• sexual side effects, including compulsive sexual behaviors
• metabolic abnormalities such as type 2 diabetes and lipid disturbances
• elevated risk of stroke
• tardive dyskinesia, causing involuntary movements
• neuroleptic malignant syndrome (NMS), a rare but severe reaction with rapid heart rate, high fever, and muscle stiffness
• low white blood cell count
• orthostatic hypotension (sudden blood pressure drop when standing), which can cause fainting and falls
• seizures
• trouble regulating body temperature
• difficulty swallowing
• slowed thinking or reflexes, which may impair driving or operating machinery
• boxed warnings: increased risk of death in older adults with dementia-related psychosis; increased risk of suicidal thoughts or behaviors in people 24 and younger
• allergic reactions, which were not reported in the clinical trials but can still occur

See the “Side effect focus” section for further details on boxed warnings and allergic reactions.

Note: If you have symptoms suggestive of a severe side effect like NMS, seek emergency care immediately.

Side effect focus

More detail on several notable side effects of Rexulti is provided below.

Boxed warnings

Rexulti carries boxed warnings—the FDA’s strongest safety alerts for medications. Details follow.

Risk of death in older adults with dementia-related psychosis: Generally, Rexulti is not recommended for older adults (65+) with psychosis related to dementia. However, it may be used in older patients specifically to treat agitation due to dementia from Alzheimer’s disease. Studies have found an increased risk of death in older adults with dementia-related psychosis, often due to cardiovascular events or infections.

Psychosis can involve disturbances such as:

• hallucinations (seeing or hearing things that aren’t present)
• delusions (false beliefs)
• depression
• anxiety

Dementia involves declines in mental function, which may include:

• memory loss
• changes in language, thought, speech, or behavior

Risk of suicidal thoughts or behaviors: Antidepressants can raise the risk of suicidal ideation and behavior in children and adults up to age 24. Rexulti is classified as an atypical antipsychotic rather than an antidepressant, but it’s used together with antidepressants to treat MDD.

The FDA has not approved Rexulti for pediatric depression but it may be prescribed for schizophrenia in patients 13 years and older.

If you have a history of suicidal thoughts or self-harm, discuss this with your prescriber before starting Rexulti so you can weigh the risks and benefits.

What may help

The reason for the increased mortality risk in older adults with dementia-related psychosis is not fully understood. Other health issues and concomitant medications can also influence risk. If you’re worried, ask your doctor about whether Rexulti is a safe choice for you.

Rexulti can also elevate the risk of suicidal thoughts or behaviors, particularly in those with a prior history of mood disorders. Share your full psychiatric history with your clinician before starting Rexulti.

Help is out there

If you or someone you know is in crisis or thinking about suicide, get help:

• Call or text the 988 Suicide and Crisis Lifeline at 988 or chat at 988lifeline.org. Counselors are available 24/7 for free, confidential support.
• Text HOME to the Crisis Text Line at 741741 to connect with a trained volunteer for free, confidential help round-the-clock.
• If you’re outside the U.S., find local helplines through Befrienders Worldwide.
• If it’s safe to do so, call 911 or your local emergency number.

If you’re calling on behalf of someone else, remain with them until help arrives. Remove dangerous items if you can do so safely. If not in the same location, stay on the phone with them until assistance arrives.

Allergic reaction

Although allergic reactions to Rexulti were not observed in the clinical trials, they can still occur.

Milder allergic signs may include:

• skin rash
• itching
• flushing (temporary warmth, redness, or deepening of skin tone)

Severe allergic reactions are rare but may produce swelling beneath the skin—often around the eyelids, lips, hands, or feet—and swelling of the tongue, mouth, or throat, which can impair breathing.

Contact your prescriber if you suspect an allergic reaction to Rexulti. In a suspected emergency, call 911 or your local emergency number immediately.

Is Rexulti used for depression?

Yes. For adults with major depressive disorder (MDD), Rexulti may be prescribed as an adjunct to an antidepressant. Read on for details about this indication; other uses are discussed later.

Short-term sadness is normal, but MDD involves persistent and intense low mood that significantly affects daily life, sleep, and functioning.

For MDD, Rexulti is given in combination with an antidepressant—this is called adjunctive therapy.

Rexulti is part of the second-generation (atypical) antipsychotic class, which generally carry fewer serious side effects than older antipsychotics. It’s believed Rexulti helps alleviate depressive symptoms by modulating brain chemicals.

Discuss the advantages and disadvantages of using Rexulti for MDD with your healthcare provider.

Does Rexulti have other uses?

Yes. Rexulti is also prescribed for schizophrenia and for agitation due to Alzheimer’s-related dementia in adults. (Its use for depression is covered in the preceding section.)

Rexulti for schizophrenia

Rexulti is indicated for schizophrenia in adults and in adolescents aged 13 years and older.

Symptoms of schizophrenia can vary and may include:

• intrusive or disordered thoughts
• movement abnormalities
• hallucinations
• agitation
• sleep disturbances
• disorganized speech

Research indicates that schizophrenia is associated with imbalances in neurotransmitters. Rexulti is thought to act in part by modulating dopamine and serotonin activity.

Your provider can explain the potential benefits and risks of Rexulti for schizophrenia in your specific case.

Rexulti for agitation

Rexulti is approved to treat agitation in adults when it is due to dementia from Alzheimer’s disease.

Agitation may present as restlessness, irritability, and excessive worry. Triggers can include stress, medications, or underlying medical issues.

This indication is specific to agitation caused by Alzheimer’s-related dementia—a progressive condition that impairs memory, thinking, and communication and usually affects older adults.

Rexulti for agitation is intended for daily dosing rather than intermittent, symptom-triggered use.

The mechanism for reducing agitation is not fully defined, but modulation of dopamine and serotonin is thought to play a role.

The precise mechanism of Rexulti is not fully understood, but it is believed to act by modulating neurotransmitters—particularly dopamine and serotonin—to help reduce symptoms of the conditions it treats.

What is Rexulti’s dosage?

Your healthcare provider will prescribe the dose that’s best for you. The information below outlines commonly used dosing regimens, but always follow the dose your clinician prescribes.

Form and strengths

Rexulti is supplied as oral tablets in the following strengths:

• 0.25 milligrams (mg)
• 0.5 mg
• 1 mg
• 2 mg
• 3 mg
• 4 mg

Recommended dosages

Your Rexulti dose will depend on factors including:

• the condition being treated
• your age
• your response to the medication
• concomitant medications
• side effects you experience
• other health problems (like liver or kidney disease)
• how you metabolize certain drugs

The dosages below are for adults; see the “Children’s dosage” section for pediatric recommendations.

Dosage for depression

For MDD, Rexulti is taken once daily alongside an antidepressant.

Typically, clinicians start at a low dose (for example, 0.5 mg) and monitor response, increasing the dose after several weeks if needed.

The maximum recommended dose for depression is 3 mg once daily.

Dosage for schizophrenia

For schizophrenia, a common initiation schedule is 1 mg once daily on days 1–4, increasing to 2 mg once daily on days 5–7. If necessary, further increases may begin on day 8.

The maximum dose for schizophrenia is 4 mg once daily.

Dosage for agitation

For agitation related to Alzheimer’s dementia, the usual start is 0.5 mg once daily for days 1–7, then increased to 1 mg once daily for days 8–14. If needed, further increases may begin on day 15.

The maximum dose for this indication is 3 mg once daily.

Children’s dosage

Rexulti may be prescribed for schizophrenia in adolescents aged 13 and older. A typical pediatric initiation is 0.5 mg once daily for 4 days, then 1 mg once daily on days 5–7, with possible further increases starting on day 8.

The maximum pediatric dose for schizophrenia is 4 mg once daily.

How is Rexulti taken?

Rexulti is swallowed as a tablet.

Taking Rexulti with other drugs

For MDD, Rexulti is used together with an antidepressant. Examples of antidepressants that may be combined with Rexulti include:

• paroxetine (Paxil)
• sertraline (Zoloft)
• venlafaxine (Effexor XR)
• vortioxetine (Trintellix)
• duloxetine (Cymbalta)

For schizophrenia, Rexulti may be used alone or alongside other therapies. For agitation due to Alzheimer’s dementia, it’s generally used alone.

Discuss your overall treatment regimen and any co-prescribed medications with your prescriber.

Questions about taking Rexulti

Common practical questions about Rexulti include:

• What if I miss a dose? If you miss a dose, take it as soon as you remember unless it’s almost time for the next dose. Do not double the next dose. If it’s near your usual dosing time, skip the missed dose and continue your regular schedule. Using reminders can help maintain consistency.
• Will I need long-term treatment? There’s no fixed duration for Rexulti therapy. You and your clinician will decide based on how well the medication controls your symptoms.
• Can Rexulti be chewed or split? No. Swallow Rexulti tablets whole. Crushing, chewing, or splitting can alter how the medication is released and absorbed. If you have difficulty swallowing tablets, ask your clinician or pharmacist for advice.
• Should I take Rexulti with food? You may take Rexulti with or without food; food does not significantly affect its absorption.
• How soon will Rexulti work? It may take several days to a few weeks to notice improvement. Response time varies by individual and condition. Ask your clinician what to expect for your situation.

Questions for your doctorPrepare questions before appointments, such as: How might Rexulti affect my body, mood, or daily routine? Consider bringing a support person to help you recall information. If you don’t understand something, ask your clinician to clarify. Healthcare providers aim to help you get effective care, so share concerns and feedback openly.

What should I know about Rexulti vs. Abilify?

Both Rexulti and Abilify are atypical (second-generation) antipsychotics. They share some uses and side effect profiles but differ in active ingredient and some specific properties. Rexulti’s active ingredient is brexpiprazole, whereas Abilify contains aripiprazole.

Both medications are used for depression adjunctive therapy and schizophrenia, among other uses.

Both are available as oral tablets. Abilify additionally has long-acting injectable versions marketed as Abilify Maintena and Abilify Asimtufii, which provide slow release of the drug over time and are not used for every Abilify indication.

Talk with your clinician if you want a comparison of which medication might be more appropriate for you.

What should I know about Rexulti vs. Latuda?

Rexulti and Latuda are both atypical antipsychotics but contain different active ingredients: brexpiprazole (Rexulti) and lurasidone hydrochloride (Latuda).

Both treat schizophrenia in adults and appropriate pediatric groups. Rexulti is also approved as add-on therapy for MDD in adults and for agitation due to Alzheimer’s-related dementia. Latuda is approved for depressive episodes associated with bipolar I disorder in adults and some children and may be co-prescribed with lithium or valproate for that indication.

Consult your prescriber to determine which medication is best suited to your condition.

How does Rexulti compare with Vraylar and Seroquel?

Rexulti, Vraylar (cariprazine), and Seroquel (quetiapine) are all atypical antipsychotics with overlapping but distinct indications and formulations.

Seroquel is also available as an extended-release formulation (Seroquel XR), which treats similar conditions and can be used as adjunctive therapy for depression. Rexulti or Seroquel may be used in some pediatric situations; Vraylar is generally prescribed for adults.

Ask your provider for more details comparing these options and the trade-offs for your situation.

What are some frequently asked questions about Rexulti?

Below are answers to common questions about Rexulti.

Will I have withdrawal symptoms if I stop taking Rexulti?

No. Rexulti does not produce physical dependence, so abrupt discontinuation does not cause classic withdrawal. However, stopping the medication suddenly may worsen the condition it was treating. If you plan to stop Rexulti, consult your prescriber for a safe discontinuation plan to reduce the chance of symptom recurrence.

Is Rexulti used for anxiety or bipolar disorder?

Rexulti is not FDA-approved for anxiety disorders or bipolar disorder. It may be prescribed off-label for such conditions in some cases. If you’re wondering about using Rexulti for anxiety or bipolar disorder, discuss this with your clinician, who can outline evidence and alternative treatments.

Note that Rexulti can rarely cause anxiety as a side effect; report new or worsening anxiety to your provider.

What’s the half-life of Rexulti, and how long does it stay in your system?

Brexpiprazole, Rexulti’s active ingredient, has a half-life of approximately 91 hours. It generally takes about four to five half-lives for a drug to be largely eliminated from the body, so Rexulti may remain in the system for roughly 2–3 weeks, though individual factors like genetics and organ function can influence this.

How does Rexulti work?

The precise mechanism of Rexulti is not fully understood, but it is believed to act by modulating neurotransmitters—particularly dopamine and serotonin—to help reduce symptoms of the conditions it treats.

Rexulti cost

Prescription costs vary depending on insurance coverage and pharmacy choice.

For cost-saving options, see a Rexulti cost guide or consult your prescriber or pharmacist. The Rexulti manufacturer’s website also lists potential support programs and savings cards you may qualify for.

What should be considered before taking Rexulti?

Discuss all medications and medical conditions with your clinician before starting Rexulti.

Mention if you have kidney or heart disease, diabetes, high cholesterol or triglycerides, a history of seizures, or other medical issues.

If you are pregnant, planning pregnancy, or breastfeeding, inform your prescriber. Antipsychotics may carry risks during pregnancy and breastfeeding.

Further considerations are outlined below.

Interactions

Drugs, vaccines, and certain foods can interact with Rexulti, altering its effects.

Always tell your clinician about all prescription and over-the-counter drugs, vitamins, herbs, and supplements you use. Your clinician or pharmacist can advise on potential interactions with Rexulti.

Interactions with drugs or supplements

Rexulti is metabolized by liver enzymes. Medications that affect those enzymes can increase or decrease Rexulti levels. Some drugs may raise Rexulti concentrations and might require a lower dose, including:

• certain antidepressants such as bupropion (Wellbutrin SR/XL), paroxetine (Paxil), and duloxetine (Cymbalta)
• certain antifungals like fluconazole (Diflucan)
• quinidine (for heart rhythm disorders)
• certain antibiotics such as clarithromycin

Other drugs can accelerate Rexulti’s clearance, potentially reducing its effectiveness; in such cases, your clinician may need to increase the dose. Examples include:

• rifampin (an antibiotic)
• anticonvulsants like carbamazepine (Tegretol, Equetro) and phenytoin (Phenytek, Dilantin)

This is not a complete list. See a Rexulti interactions resource or speak with your clinician or pharmacist for comprehensive information.

Other interactions

Certain herbs and supplements can also affect Rexulti. For example, St. John’s wort, often used for depressive symptoms, may decrease Rexulti’s effectiveness and should not be used concurrently. Tell your clinician about any herbal products you take.

Boxed warnings

Rexulti carries boxed warnings. These include increased mortality risk in older adults with dementia-related psychosis and the potential for increased suicidal thoughts or behaviors in those 24 and younger when used with antidepressants. See the earlier “What are Rexulti’s side effects?” section for more on these warnings.

Other warnings

Rexulti can have harmful effects in people with certain underlying conditions. Discuss your full medical history with your clinician, especially if you have:

• liver disease
• previous allergic reactions
• difficulty metabolizing drugs
• kidney disease
• diabetes
• heart or blood pressure issues
• seizure disorders
• abnormal cholesterol levels
• low white blood cell count
• trouble regulating body temperature
• fall risk
• slowed thinking, reflexes, or excessive sedation that could impair driving or machinery operation

Use with alcohol

Combining alcohol with Rexulti may worsen certain side effects such as drowsiness and movement issues, and may affect liver function. If you consume alcohol, ask your clinician whether it’s safe to continue drinking while on Rexulti.

Pregnancy and breastfeeding

If you could be pregnant or are breastfeeding, discuss Rexulti’s risks and benefits with your clinician. Use during the third trimester may increase the risk of movement or withdrawal signs in exposed newborns. The safety of Rexulti during breastfeeding is not well established.

What should be done in case of overdose?

Take only the dose prescribed by your clinician. Overdosing can cause serious adverse effects. See the “What are Rexulti’s side effects?” section for potential consequences.

What to do if you take too much Rexulti

If you suspect an overdose, contact your prescriber. You can also call 800-222-1222 to reach America’s Poison Centers or use its online resource. If severe symptoms are present, call 911 or go to the nearest emergency department immediately.

Ask a pharmacist

Q:

Will I need to stop Rexulti if I’m prescribed an antibiotic?

A:

It depends on the antibiotic. Most antibiotics are compatible with Rexulti, but some can increase Rexulti levels and raise the risk of adverse effects. In such cases, your clinician might advise temporarily stopping Rexulti while you complete the antibiotic course.

Antibiotics known to interact with Rexulti include:

• clarithromycin
• erythromycin (Ery-Tab)

Topical formulations (for example, erythromycin eye ointment) are less likely to interact with Rexulti.

If a clinician prescribes an antibiotic, make sure they know you are taking Rexulti so they can check for interactions and choose a safe option.

Disclaimer: Efforts have been made to ensure the accuracy and timeliness of the information presented. This article is not a substitute for professional medical advice. Always consult your healthcare provider before starting, stopping, or changing any medication. Drug information can change, and not all possible uses, directions, precautions, warnings, interactions, allergic reactions, or adverse effects are included here. The absence of specific warnings does not imply that a drug or combination is safe or appropriate for all patients or uses.